Dataset Information
Hypermetabolism, hyperphagia, and reduced adiposity in tankyrase-deficient mice.
Ontology highlight
ABSTRACT: Objective
Tankyrase (TNKS) is a Golgi-associated poly-ADP-ribose polymerase that is implicated in the regulation of GLUT4 trafficking in 3T3-L1 adipocytes. Its chromosomal locus 8p23.1 is linked to monogenic forms of diabetes in certain kindred. We hypothesize that TNKS is involved in energy homeostasis in mammals.Research design and methods
Gene-trap techniques were used to ablate TNKS expression in mice. Homozygous and wild-type littermates maintained on standard chow were compared.Results
Wild-type mice express the TNKS protein abundantly in adipose tissue, the brain, and the endocrine pancreas but scarcely in the exocrine pancreas and skeletal muscle. TNKS-deficient mice consume increased amounts of food (by 34%) but have decreased plasma leptin levels and a >50% reduction in epididymal and perirenal fat pad size. Their energy expenditure is increased as assessed by metabolic cage studies and core body temperatures. These changes are not attributable to an increase in physical activity or uncoupled respiration (based on oxygraph analyses of mitochondria isolated from brown fat and skeletal muscle). The heightened thermogenesis of TNKS-deficient mice is apparently fueled by increases in both fatty acid oxidation (based on muscle and liver gene expression analyses and plasma ketone levels) and insulin-stimulated glucose utilization (determined by hyperinsulinemic-euglycemic clamps). Although TNKS deficiency does not compromise insulin-stimulated GLUT4 translocation in primary adipocytes, it leads to the post-transcriptional upregulation of GLUT4 and adiponectin in adipocytes and increases plasma adiponectin levels.Conclusions
TNKS-deficient mice exhibit increases in energy expenditure, fatty acid oxidation, and insulin-stimulated glucose utilization. Despite excessive food intake, their adiposity is substantially decreased.
SUBMITTER: Yeh TY
PROVIDER: S-EPMC2768175 | biostudies-literature | 2009 Nov
REPOSITORIES: biostudies-literature
Publications
Hypermetabolism, hyperphagia, and reduced adiposity in tankyrase-deficient mice.
Diabetes 20090803 11
<h4>Objective</h4>Tankyrase (TNKS) is a Golgi-associated poly-ADP-ribose polymerase that is implicated in the regulation of GLUT4 trafficking in 3T3-L1 adipocytes. Its chromosomal locus 8p23.1 is linked to monogenic forms of diabetes in certain kindred. We hypothesize that TNKS is involved in energy homeostasis in mammals.<h4>Research design and methods</h4>Gene-trap techniques were used to ablate TNKS expression in mice. Homozygous and wild-type littermates maintained on standard chow were comp ...[more]